This investigation will establish that relatively low concentrations of bradykinin can stimulate the proliferative rate of a macrophage cell line. Although well known for its inflammation-inducing properties, the nonapeptide hormone has heretofore not been recognized as a growth factor. Preliminary evidence suggests that it enhances proliferation of the macrophage cell line, P388D1. Therefore, bradykinin may be a physiological nitrogen for macrophages during inflammation and/or bradykinin may be a factor in proliferative disorders characterized by chronic inflammation and high bradykinin concentrations. In the latter case, bradykinin could contribute to the hypertrophy of synovial membrane cells observed in connective tissue disorders such as rheumatoid arthritis. This investigation will also determine the significance of bradykinin in the proliferation of normal mouse macrophages. Cell proliferation will be determined by cell counts, uptake of 3H-thymidine, and total protein content. Recent studies suggest that prostaglandins are not responsible for the bradykinin-induced proliferation of cells. Indeed bradykinin-stimulated prostaglandins probably act as negative feedback inhibitors of proliferation. Experiments using inhibitors of prostaglandin biosynthesis, prostaglandin administration, and measurement of cell production by the prostaglandins will determine the relationship between bradykinin and prostaglandins on cell proliferation. A comparative proliferation study of WI-38 lung fibroblasts, which possess normal prostaglandin biosynthetic ability, and a virally transformed WI-38 cell line, which produces little prostaglandin, will determine the significance of a broad interpretation regarding bradykinin and prostaglandin effects on cell proliferation.